THERMAL TECHNIQUE AND DIFFERENTIAL SCANNING CALORIMETRY

DSC --PRINCIPLE, DSC CURVE, ADVANTAGES, DISADVANTAGE AND APPLICATION

1. Thermal Techniques & Differential scanning calorimetry Presenter: Amruta Balekundri M.Pharm 1 st semester, Department of Pharmaceutical Quality Assurance, KLE College of Pharmacy, Belagavi. 1

2. Contents: Introduction Thermal Analysis Differential scanning calorimetry History of DSC Principle of DSC Typical DSC curve Instrumentation Calibration Advantages Disadvantages Application 2

3. Thermal analysis: Thermal analysis refers to any technique for the study of materials which involves thermal control. Measurements are usually made with increasing temperature, but isothermal measurements or measurements made with decreasing temperatures are also possible . 3

4. Thermal analysis: In fact, any measuring technique can be made into a thermal analysis technique by adding thermal control. Simultaneous use of multiple techniques increases the power of thermal analysis, and modern instrumentation has permitted extensive growth of application . The basic theories of thermal analysis (equilibrium thermodynamics, irreversible thermodynamics and kinetics) are well developed 4

5. Types of Thermal analysis: 5

6. Common Thermal Analysis Methods and the Properties Measured: 6

7. Differential scanning calorimetry: 7

8. History of DSC The technique was developed by E. S. Watson and M. J. O'Neill in 1962 , introduced commercially in 1963 at Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. First Adiabetic differential scanning calorimeter that could be used in Biochemistry was developed by P.L.Privalov in 1964. 8

9. Differential scanning calorimetry: Principle: It is a technique in which the energy necessary to establish a zero temp. difference between the sample & reference material is measured as a function of temp. Here, sample & reference material are heated by separate heaters in such a way that their temp are kept equal while these temp. are increased or decreased linearly 9

10. Differential scanning calorimetry: Endothermic reaction: if sample absorbs some amount of heat during phase transition then reaction is said to be endothermic. In endothermic reaction more energy needed to maintain zero temp difference between sample & reference. E.g. Melting, boiling, sublimation, vaporization, de-solvation Exothermic reaction: if sample released some amount of heat during phase transition, then reaction is said to be exothermic. In exothermic reaction, less energy needed to maintain zero temp difference between sample & reference . E.g crystallization, degradation, polymerization. 10

11. Differential scanning calorimetry: DSC Is widely used to measure glass transition temp & characterization of polymer. Glass Transition temp( Tg ): Temp at which an amorphous polymer or an amorphous part of crystalline polymer goes from hard ,brittle state to soft, Rubbery state. 11

12. Instrumentation: There are five different types of DSC instrument: Heat flux DSC Power compensated DSC Modulated DSC Hyper DSC Pressure DSC 12

13. 1.Heat flux DSC: In heat flux DSC, the difference in heat flow into the sample and reference is measured while the sample temperature is changed at the constant rate. The main assembly of the DSC cell is enclosed in a cylindrical, silver heating black, which dissipates heat to the specimens via a constantan disc which is attached to the silver block . The disk has two raised platforms on which the sample and reference pans are placed. 13

14. 1.Heat flux DSC: A chromel disk and connecting wire are attached to the underside of each platform, and the resulting chromel -constantan thermocouples are used to determine the differential temperatures of interest . Alumel wires attached to the chrome discs provide the chromel-alumel junctions for independently measuring the sample and reference temperature. A separate thermocouple embedded in the silver block serves a temperature controller for the programmed heating cycle. And inert gas is passed through the cell at a constant flow rate of about 40 ml/min . 14

15. Heat flux DSC: Schematic representation: 15

16. 1.Heat flux DSC: In heat flux DSC, we can write the total heat flow dH / dt as, dH / dt = Cp dT / dt + f ( T,t ) Where, H = enthalpy in J mol-1 Cp =specific heat capacity in JK -1 mol-1 f ( T,t )= kinetic response of the sample in J mol-1 Thus , the total heat flow is the sum of the two terms, one related to the heat capacity, and one related to the kinetic response . 16

17. Types of heat flux DSC: 17

18. A.The Disk Type Measuring System– Heat Flux DSC : The disk type measuring system heat exchange takes place trough a disk which is solid sample support. The main heat flow from the furnace passes symmetrically trough disk with a medium thermal conductivity; this is its main characteristic. In some cases the disks are made with combination of metal (e.g. platinum) and covered with ceramics. Modification of the disk type of DSC is very common. 18

19. A.The Disk Type Measuring System– Heat Flux DSC : One is HF-DSC with a triple measuring system. With three separate locations the measurement of specific heat is measured with just one run . In the classic HF-DSC device three measurements must be made (with an empty crucible, with a sapphire or a known inert sample and with the investigated sample). Another modification is high pressure HF-DSC, which is used to determine vapour pressures and heats of evaporation. Its features are high sensitivity and small sample volume 19

20. A.The Disk Type Measuring System– Heat Flux DSC :Schematic representation 20

21. B.The Cylinder measuring system – Heat flux DSC: In the cylinder type measuring system the heat exchange takes place between the(big) cylindrical sample cavities and the furnace with a low thermal conductivity (thermopile ). Only low heating and cooling rates are possible. The sensitivity per unit volume is high even with a large sample volume. This system has a larger time constant than the first two measuring systems. The heat flux DSC operating on Calvet principle is using a cylinder type measuring system by two sintered alumina cylinders set parallel and symmetrical in the heating furnace. 21

22. B.The Cylinder measuring system – Heat flux DSC: The crucible used here is produced from stainless steel. The HF-DSC with the cylinder measuring system is appropriate for large samples. Compared with the other apparatuses, the cylinder type has a much larger volume and therefore a longer time constant which can be as long as 40. min 22

23. B.The heat flux DSC with a cylinder- type measuring System ( Calvet ): 23

24. C.The turret-type measuring system – HF DSC : In turret type heat exchange takes place via small hollow cylinders which also serve as sample support. Small hollow cylinders are used for sample support and for the heat exchange . The turret measuring system is ideal for determining the purity of metals. The advantage of the turret system is in the heat transfer from the jacket to the sample, because it goes through a thin-walled cylinder. This way a very short heat conducting path is achieved 24

25. C.The turret-type measuring system – HF DSC : The system is very small thus the characteristic time is very short. No interference between the sample and the present. The turret type is special because of a third thermocouple which measures the thermal inertia. This is a so-called Tzero DSC technology 25

26. C.The turret type measuring system HF-DSC 26

27. D.Micro differential DSC–modified HF DSC : This method is a combination of an isothermal calorimeter and a HF-DSC mode device. In an isothermal calorimeter, the heat generated by the sample, flows through the thermal resistance into a water jacket. The temperature difference across the thermal resistance is measured. Micro DSC has the same ability to measure the thermal properties as an ordinary DSC device. 27

28. D.Micro differential DSC–modified HF DSC : One of the advantages is a very high sensitivity but on the other hand the temperature range is very narrow (–20 °C to ≈120°C). With this type of device it is ideal to study crystallisation because the cooling and heating rates can be even lower than 0.001 °C/min (with a response time of few seconds) and is also suitable to determine phase transitions like intermediate phases between solid and liquid in Liquid crystals 28

29. D.The heat flux Micro differential DSC: 29

30. 2.Power compensation DSC : In power compensation DSC, the temperatures of the sample and reference are kept equal to each other while both temperatures are increased or decreased linearly. The power needed to maintain the sample temperature equal to the reference temperature is measured. In power compensation DSC two independent heating units are employed . These heating units are quite small, allowing for rapid rates of heating, cooling and equilibration. The heating units are embedded in a large temperature- controlled heat sink. 30

31. 2.Power compensation DSC : The sample and reference holders have platinum resistance thermometers to continuously monitor the temperature of the materials. Both sample and reference are maintained at the programmed temperature by applying power to the sample and reference heaters. The instrument records the power difference needed to maintain the sample and reference at the same temperature as a function of the programmed temperatures . 31

32. 2.Power compensation DSC : Power compensated DSC has lower sensitivity than heat flux DSC, but its response time is more rapid. This makes power compensated DSC well suited for kinetics studies in which fast equilibrations to new temperature settings are needed. it is also capable of higher resolution then heat flux DSC 32

33. 2.Power compensation DSC : All PC DSC are in basic principles the same. But, one of the special PC DSC is photo DSC. Where direct measurements of radiation flow occur under a light source. This way the degradation of material can also be observed. The maximum heating rate for not modified PC DSC is up to 500K/min and the maximum cooling rate is up to 400 K/min. Temperature range of measurement is up to 400 °C with time constant of only 1.5 s or lower. Sample masses are around 20 mg. Crucibles of different volumes (lower than several ten cubic millimeter's) are made mostly of aluminum 33

34. Power compensation DSC : 34

35. 3.Modulated DSC Modulated DSC uses the same heating and cell arrangement as the heat – flux DSC method. it is a new technique introduced in 1993 . The main advantage of this technique is the separation of overlapping events in the DSC scans. In MDSC the normally linear heating ramp is overlaid with the sinusoidal function (MDSC) defined by a frequency and amplitude to produce a sine wave shape temperature versus time function . Using Fourier mathematics, the DSC signal is split into two components: reflecting no reversible events (kinetic) and reversible events 35

36. 3.Modulated DSC: T = T0= bt+B sin( wt ) dq / dt =C [ b+Bw cos( wt )] +f( t,T )+K sin ( wt ) where, T=temperature C=specific heat t=time w=frequency f( t,T )= the average underling kinetic function once the effect of the sine wave modulation has been subtracted . K= amplitude of the kinetic response to the sine wave modulation . [ b+Bw cos ( wt )]=the measured quantity dT / dt or reversing Curve. 36

37. 3.Modulated DSC: MDSC is a valuable extension of conventional DSC. Its applicability is recognized for precise determination of the temperature of glass transition and for the study of the energy of relaxation . It has been applied for the determination of glass transition of Hydroxypropylmethylcellulose films and for the study of amorphous lactose as well as some glassy drugs 37

38. 4.Hyper DSC: The high resolution of PC-DSC or new type of power compensating DSC provides the best results for an analysis of melting and crystallization of metals or detection of glass transition temperature ( Tg ) in medications. Fast scan DSC has the ability to perform valid heat flow measurements with fast linear controlled rates (up to 500 K/min) especially by cooling, where the rates are higher than with the classical PC DSC. Standard DSC operates under 10 K/ min. 38

39. 4.Hyper DSC: The benefits of such devices are increased sensitivity at higher rates (which enables a better study of the kinetics in the process), suppression of undesired transformation like solid – solid transformation etc . It has a great sensitivity also at a heating rate of 500 K/min with 1 mg of sample material. This technique is especially proper for the pharmaceutics industry for testing medicaments at different temperatures where fast heating rates are necessary to avoid other unwanted reactions etc 39

40. 5.Pressure DSC In pressure DSC, the sample can be submitted to different pressures, which allows the characterization of substances at the pressures of processes or to distinguish between overlapping peaks. Applications of this technique includes studies of pressure sensitive reactions, evaluation of catalysts , and resolution of overlapping transitions. 40

41. Typical DSC Curve: 41

42. Typical DSC Curve: The result of a DSC experiment is a curve of heat flux versus temperature or versus time. There are two different conventions: exothermic reactions in the sample shown with a positive or negative peak, depending on the kind of technology used in the experiment. This curve can be used to calculate enthalpies of transitions. This is done by integrating the peak corresponding to a given transition. 42

43. Typical DSC Curve: It can be shown that the enthalpy of transition can be expressed using the following equation: △H = KA where H is the enthalpy of transition, K is the calorimetric constant, and A is the area under the curve. The calorimetric constant will vary from instrument to instrument, and can be determined by analyzing a well-characterized sample with known enthalpies of transition. 43

44. Factors Affecting DSC Curve: Instrumental factors : Furnace heating rate Recording or chart speed Furnace atmosphere Geometry of sample holder/location of sensors Sensitivity of the recording system Composition of sample containers 44

45. Factors Affecting DSC Curve: Sample characteristics: Amount of sample Nature of sample Sample packing Solubility of evolved gases in the sample Particle size Heat of reaction Thermal conductivity 45

46. Experimental Parameters: Sample preparation Experimental conditions Calibration Resolution Sources of errors 46

47. 1.Sample Preparation: Sample Types: The DSC can be used to analyze virtually any material that can be put into a DSC sample pan. This includes: Films Fibers Powders Solutions Composites When making quantitative measurements or verifying reproducibility, it is important to ensure good thermal contact between the sample and sample pan. The physical characteristics of the sample affect the quality of this contact. 47

48. 1.Sample Preparation: When using powdered or granular samples, spread them evenly across the bottom of the pan to minimize thermal gradients. For solid samples, select the side of your sample with the flattest surface for contact with the pan.  After encapsulating the sample, ensure that the pan bottom is flat.  If it is not, flatten it by pressing the pan bottom on a flat surface. NOTE:  The contact between the pan and the raised sample platform  is as important as the contact between the sample and sample pan. 48

49. 1.Sample Preparation: NOTE:  The oils on your fingers can affect the results of thermal analysis experiments. Always use tweezers when handling sample pans and sample material.‘ If you overfill a pan, the heating or cooling procedures may cause the sample to boil out, buckle, or explode the pan. If you are using an Auto-sampler and this occurs so that the Auto-sampler cannot remove a pan from the cell because of deformation or boiled-out material, operation is halted until the problem is corrected. Therefore, you should be reasonably familiar with the effects of heating and cooling procedures on your samples and pans 49

50. Determining sample size: Normally, sample weight in DSC experiments is in the range of 5 to 20 milligrams.  If purity determinations are to be performed, then sample sizes of 1 to 3 milligrams are recommended.   Refer to the table below to guide you when selecting the sample size and heating rates for your experiment. 50

51. Determining sample size: Type of Measurement Sample Size (mg) Heating Rate (°C/min)   Glass transition 10 to 20 10 to 20 Melting point 2 to 10 5 to 10 Kinetics (Borchardt and Daniels) 5 to 10 5 to 20 Kinetics (ASTM) 2 to 5* 0.5 to 20 Heat capacity 10 to 70 20** Purity 1 to 3 0.5 to 1 Crystallinity or oxidative stability 5 to 10   5 to 10   MDSC 2 to 10 1 to 5 51

52. Selecting a sample pan: Selection of the appropriate DSC sample pan and lid is a very important element of your method development process. The results you obtain from the use of DSC will be affected by your choices. 52

53. Selecting a sample pan: Pan Type Pan Lid Die Set Software Pan Type Application Tzero Aluminum Tzero Pan Tzero Lid Black Tzero Aluminum Basic DSC/MDSC applications Tzero Hermetic Aluminum   Tzero Pan   Tzero Hermetic Lid Blue Tzero Hermetic Aluminum DSC applications which require hermetic seals Tzero Hermetic  Aluminum Alodined Tzero Alodined Pan Tzero Hermetic Alodined Lid Blue Tzero Hermetic Aluminum Alodined DSC applications which require hermetic seals and may evolve water Tzero Low-Mass Aluminum Tzero Low-Mass Pan Tzero Lid Black Tzero Aluminum High-sensitivity for low mass of sample 53

54. 2. Experimental conditions Heating Rate Samples are heated at a rate of 10 or 20°C/min in most cases. • Lowering the heating rates is known to improve the resolution of overlapping weight losses. Advances in the technology have made it possible for variable heating rates (High Resolution TGA) to improve resolution by automatically reducing the heating rate during periods of weight loss. 54

55. 2. Experimental conditions: Purge gas Nitrogen is the most common gas used to purge samples in TGA due to its inert nature. Whereas, helium provides the best baseline. Air is known to improve resolution because of a difference in the oxidative stability of components in the sample. Vacuum may be used where the sample contains volatile components, which helps improve separation from the onset of decomposition since the volatiles come off at lower temperatures in vacuum. • e.g. oil in a rubber tire product 55

56. 3.(a)DSC Calibration baseline: Evaluation of the thermal resistance of the sample and reference sensors measurements over the temperature range of interest 2-step process: The temperature difference of two empty crucibles is measured. The thermal response is then acquired for a standard material, usually sapphire, on both the sample and reference platforms 56

57. 3.(a)DSC Calibration baseline: Organic compounds have been recommended as standards when studying organic material to minimize differences in thermal conductivity, heat capacity, and heat of fusion and may be used predominantly at temperatures below 300 K. Amplified DSC signal is automatically varied with temperature to maintain a constant calorimetric sensitivity with temperature. 57

58. 3(b).DSC Calibration temperature: Goal is to match the melting onset temperatures indicated by the furnace thermocouple readouts to the known melting points of standards analyzed by DSC Should be calibrated as close to the desired temperature range as possible. Heat flow :use of calibration standards of known heat capacity, such as sapphire, slow accurate heating rates (0.5–2.0 °C/min), and similar sample and reference pan weights 58

59. 3(b).DSC Calibration temperature: Calibrants : high purity accurately known enthalpies thermally stable light stable Non-hygroscopic Un-reactive (pan, atmosphere) Metals: In °C; J/g Sn °C Al ° Ci 59

60. 3(b).DSC Calibration temperature: Inorganics KNO °C KClO °C Organics polystyrene 105 °C benzoic acid °C; J/g anthracene 216 °C; J/g 60

61. 4 .Resolution : One of the most important performance characteristics of a DSC instrument is its resolution. This refers to the ability of the DSC to separate or resolve closely occurring thermal transitions. The resolution of a DSC cell is dependent upon its particular design properties including the mass of the furnace, the temperature measuring system employed and the response time of the cell. 61

62. 4.Resolution: The low mass of the Pyris 1 DSC along with the use of a platinum resistance thermometer (PRT) temperature measuring system provides outstanding inherent resolution. The resolution of a DSC is also a function of the given experimental conditions, including: Purge gas Sample mass Heating rate 62

63. 4.Resolution: Enhanced resolution can be obtained using a helium rather than a nitrogen, air or oxygen purge, due to the significantly higher thermal conductivity of helium. Lower sample masses can provide improved resolution over larger masses. Slower heating rates will yield significantly better resolution than faster rates. 63

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65. 5.Sources of errors: Calibration Contamination Sample preparation – how sample is loaded into a pan Residual solvents and moisture. Thermal lag Heating/Cooling rates Sample mass Processing errors 65

66. Advantages of DSC: Instruments can be used at very high temperatures Instruments are highly sensitive. Flexibility in sample volume/form . Characteristic transition or reaction temperatures can be determined. High resolution obtained High sensitivity Stability of the material. 66

67. Limitations of DSC: DSC generally unsuitable for two-phase mixtures. Difficulties in test cell preparation in avoiding evaporation of volatile Solvents . DSC is generally only used for thermal screening of isolated intermediates and products . Does not detect gas generation. Uncertainty of heats of fusion and transition temperatures 67

68. Applications: Metal alloy melting temperatures and heat of fusion. Metal magnetic or structure transition temperatures and heat of transformation. Intermetallic phase formation temperatures and exothermal energies. Oxidation temperature and oxidation energy. Exothermal energy of polymer cure (as in epoxy adhesives), allows determination of the degree and rate of cure. 68

69. Applications: Determine the melting behavior of complex organic materials, both temperatures and enthalpies of melting can be used to determine purity of a material. Measurement of plastic or glassy material glass transition temperatures or softening temperatures, which change dependent upon the temperature history of the polymer or the amount and type of fill material, among other effects. Determines crystalline to amorphous transition temperatures in polymers and plastics and the energy associated with the transition. Crystallization and melting temperatures and phase transition energies for inorganic compounds. 69

70. Applications: Oxidative induction period of an oil or fat. May be used as one of multiple techniques to identify an unknown material or by itself to confirm that it is the expected material. Determine the thermal stability of a material. Determine the reaction kinetics of a material. Measure the latent heat of melting of nylon 6 in a nylon Spandex fabric to determine the weight percentage of the nylon 70

71. References: Skoog , dougla A, F James holler and timothy nieman , principles of instrumental analysis, 5 th edition New york 2001 Instrumental methods of Chemical analysis-GURDEEP R.CHATWAL http://folk.ntnu.no/deng/fra_nt/other%20stuff/DSC_manuals/QDSC/Selecting_a_Sample_Pan.htm#Selecting_a_Sample_Pan_for_the_Tzero_Press file:///H:/data0/mpat%20presentation/analysis/differential-scanning-calorimetry-a-review-11-22.pdf 71

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